Compounds for Eradicating or Inhibiting Proliferation of Cancer Stem Cells

Abstract

The present invention provides compounds of formula (I), compositions, uses thereof and methods for eradicating or inhibiting proliferation of cancer stem cells which includes killing; and/or inducing apoptosis in cancer stem cells. Included within the scope of such compounds, compositions, uses thereof and methods are those in which proliferation of cancer stem cells are selectively eradicated or inhibited.

1 . A compound of formula (I) 
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable derivative thereof for eradicating or inhibiting proliferation of cancer stem cells, wherein: 
         each R 1 , R 2  and R 3  is independently selected from halogen, C1-6haloalkyl, —CN, —NO 2 , —R, —OR, —SR, —N(R) 2 , —N(R)NR 2 , —C(NR)NR 2 , —N(R)C(O)R, C(O)RN(R) 2 , —N(R)C(O)N(R) 2 , —N(R)C(O)OR, —OC(O)N(R), —N(R)SO 2 R, —SO 2 RN(R) 2 , C(O)R, —C(O)OR, —OC(O)R, —C(O)OR, —S(O)R, or —SO 2 R; 
         each R is independently selected from H, or an optionally substituted group selected from C1-6 aliphatic, a 3-12 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-12 membered bicyclic aromatic carbocyclic ring; a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and 
         R 4  is independently selected from —R, —CN, halogen, C1-6 haloalkyl, —NO 2 , —SR, —N(R) 2 , —N(R)NR 2 , —C(NR)NR 2 , —N(R)C(O)R, C(O)RN(R) 2 , —N(R)C(O)N(R) 2 , —N(R)C(O)OR, —OC(O)N(R), —N(R)SO 2 R, —SO 2 RN(R) 2 , C(O)R, —C(O)OR, —C(O)OR, —S(O)R, or —SO 2 R; 
         each R is independently selected from H, or an optionally substituted group selected from C1-6 aliphatic, a 3-12 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-12 membered bicyclic aromatic carbocyclic ring; a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen or sulfur; and 
         each n is independently 0-5. 
       
     
     
         2 . The compound as claimed in  claim 1 , wherein the compound is a pharmaceutically acceptable derivative of compound of formula II or formula III: 
       
         
           
           
               
               
           
         
       
     
     
         3 . The compound as claimed in  claim 2 , wherein the pharmaceutically acceptable derivative of compound of formula II is a compound of formula IV or formula V: 
       
         
           
           
               
               
           
         
       
     
     
         4 . The compound as claimed in  claim 2 , wherein the pharmaceutically acceptable derivative of compound of formula III is a compound of formula VI or formula VII: 
       
         
           
           
               
               
           
         
       
     
     
         5 - 14 . (canceled)